Two major issues have been investigated: (1) the effect of aging on the generation of primary allogeneic cytolytic lymphocyte (CTL) activity in mice; and (2) the role of adhesion molecules in human in human natural killer (NK cell activity. The following findings have been made: (1) Following sensitization of BALB/C (H-2d) spleen cells with C57BL/6 (H- 2b), the expression of the perforin (Pore-forming-protein or Pfp) and at least two serine esterase genes (Cll/Granzyme B and BlO/Granzyme C) in primary CTL was shown to decline with age. Lytic activity was associated only with the CD8+ cell subset in this system, and similarly, the age-related declines in gene expression were expressed in CD8+ but not CD4+ cells following sensitization in vitro. In contrast, depletion of either CD4+ or CD8+ cells prior to sensitization decreased the generation of CTL in both young and old, demonstrating that the CD4+ cells were involved in the generation of effector cells. Mixture experiments suggested that the age-related decrement in CTL activity by spleen cells from old mice could be partially restored when CD4+ cells from young mice were tested together with CD8+ cells from old mice, suggesting that the age--related decline in CD8+ CTL may be secondary, at least in part, to an age-related alteration in the CD4+ subset. (2) Using large granular lymphocytes (LGL) purified from human peripheral blood, native (NK) lytic activity was inhibited by antibodies to LFA-1 alph (CD11a), and lymphokine (IL-2) activated killer (LAK) activity was inhibite by antibodies to both the alpha and beta chains of LFA-1. Using alkaline phosphatase treatment following immunoprecipitation of metabolically labele NK or LAK cells, it was observed that the alpha chain is phosphorylated in NK cells and the beta chain is phosphorylated in LAK cells. These data support the hypothesis that NK cells may use the LFA-1 alpha chain for signal transduction, whereas LAK cells can use both the alpha and beta chains.